Evaluation of Therapeutic Response in Spinal Muscular Atrophy Using Multispectral Optoacoustic Tomography (MSOT) and Magnetic Resonance Imaging (MRI)

University of Erlangen-Nürnberg Medical School

Status: Unknown

Conditions: Muscular Diseases; Spinal Muscular Atrophy

Treatments: Device: Multispectral Optoacoustic Tomography (MSOT) and Magnetic Resonance Imaging (MRI)

Study type: Interventional

Funder types: Other

Identifiers

NCT04262570

453_19B

Details and patient eligibility

About

This study aims to refine the capability of Multispectral Optoacoustic Tomography (MSOT) and Magnet Resonance Imaging (MRI) to characterise the molecular composition of muscle tissue non-invasively and to evaluate the therapeutic response in patients with spinal muscular atrophy (SMA) over time.

Full description

SMA is an autosomal-recessive disorder, characterized by progressive muscle weakness and atrophy with an incidence of 1/10,000. The condition is caused by a homozygous deletion or mutation in the survival motor neuron 1 (SMN1), resulting in reduced expression of the survival motor neuron (SMN) protein. This leads to the degeneration of motor neurons in the spinal cord and brain stem. A nearby related gene, survival motor neuron 2 (SMN2), could partially compensate the loss of SMN1. Individuals with a higher copy number of SMN2 do in general have a milder phenotype. New therapeutic approaches, e.g. nusinersen (spinraza©), an antisense oligonucleotide medication that modulates pre-messenger RNA splicing of the survival motor neuron 2 (SMN2) gene, are promising to help the formerly incurable disease. However, most clinical trials lack primary outcomes other than clinical testing. Preliminary work shows that new methods such as multispectral optoacoustic tomography (MSOT) and magnetic resonance imaging (MRI) detect tissue changes very sensitively. Multispectral optoacoustic tomography (MSOT) is capable of visualizing the distribution of endogenous absorbers by initiating laser-induced thermoelastic expansion and detection of resulting pressure waves. This imaging technique enables the label-free detection and quantification of different endogenous chromophores. In addition to this technology, MRI imaging has advanced in the field of muscle diseases, with 23Na-MRI being the first example. With both methods, the molecular composition of muscle tissue can be determined non-invasively and quantitatively at the same time. In this first pilot study on patients with SMA, the investigators will now assess whether the differences in the muscle composition of SMA patients with or without therapy can be quantified and whether they can be used simultaneously as markers during therapy with nusinersen (spinraza©) . Ideally, both techniques can complement or validate each other. In the future, this could generate a completely new, non-invasive method for evaluating endogenous biomarkers for therapy response.

Enrollment: 10 estimated patients

Sex: All

Ages: 14+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Genetically confirmed SMA type III
• From age 14
• Willingness and ability to participate, sufficient knowledge of the german language to understand the declaration of consent, or if not possible, information of the patient in his/her mother tongue or English
• High probability that the patients will be able to fully participate in the study (defined by the ability to lie still for about 1 hour and follow any breathing commands) For therapy arm: • Medical indication for Spinraza® therapy; start of study before first administration Spinraza® administration For control arm: • No medical indication for Spinraza® therapy

Exclusion criteria

• Pregnancy
• Tattoo on the skin area to be examined
• General contraindications for MRT examinations
• Electrical implants like pacemakers or perfusion pumps
• Pronounced claustrophobia
• Study participants with ferromagnetic or electrically conductive implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, heart valves with metal parts, metal splinters, tattoos next to the eye, symmetrical tattoos on the extremities or steel implants must consult the study physician; they may not be able to be examined (relative contraindications for MRI).
• Non-approved concomitant medication: strongly sedating medication must be excluded, as intensive monitoring of bodily functions during ongoing imaging cannot be guaranteed and the active participation of the test person might be necessary.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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10 participants in 2 patient groups

SMA patients (therapy arm)

Experimental group

Description:

* Multispectral Optoacoustic Tomography (MSOT) of muscles (left and right, total 4 sites) leg proximal: Musculus quadriceps, distal: Musculus triceps surae arm proximal: Musculus biceps, distal: forearm flexors; * Magnetic Resonance Imaging (MRI) of lower leg * Physical assessment/milestones: expanded Hammersmith functional motor scale (HFMSE)/ Revised Upper Limb Module (RULM)/ 6-minute-walking-test (6-MWT)

Treatment:

Device: Multispectral Optoacoustic Tomography (MSOT) and Magnetic Resonance Imaging (MRI)

SMA patients (control arm)

Active Comparator group

Description:

* Multispectral Optoacoustic Tomography (MSOT) of muscles (left and right, total 4 sites) leg proximal: Musculus quadriceps, distal: Musculus triceps surae arm proximal: Musculus biceps, distal: forearm flexors; * Magnetic Resonance Imaging (MRI) of lower leg * Physical assessment/milestones: expanded Hammersmith functional motor scale (HFMSE)/ Revised Upper Limb Module (RULM)/ 6-minute-walking-test (6-MWT)

Treatment:

Device: Multispectral Optoacoustic Tomography (MSOT) and Magnetic Resonance Imaging (MRI)